We propose to study the biochemical mechanism by which glucocorticoids alter collagen metabolism. A decrease in collagen content in normal and inflamed connective tissues has been reported. This decrease in collagen content may result from either an alteration of collagen synthesis and (or) degradation. Since glucocorticoids have been reported to decrease proline hydroxylase activity in sponge induced granuloma tissue, a glucocorticoid-mediated decrease in collagen synthesis is suggested. The effects of glucocorticoids on collagen biosynthesis and proline hydroxylase activity will be studied in polyvinyl sponge induced granuloma tissue in the whole animal and in granuloma tissue maintained organ culture. Studies will also be carried out to determine the mechanism by which glucocorticoids effect proline hydroxylase activity. These studies are designed to answer the following questions: 1. Is there a temporal relationship between the decreased proline hydroxylase activity and decreased collagen synthesis after glucocorticoid treatment? 2. Are the effects of glucocorticoid treatment on proline hydroxylase and collagen synthesis reversible? 3. Is the glucocorticoid mediated decrease in proline hydroxylase activity simply the result of depressed cellular metabolism? 4. What is the nature of the mechanism(s) by which glucocorticoids decrease proline hydroxylase activity?